treatment of myasthenia gravis exacerbation or crisis with efgartigimod

Conditions: Myasthenia Gravis Crisis; Myasthenia Gravis Exacerbations; AChR Myasthenia Gravis

Summary: this study plans to learn more about if the drug efgartigimod can be used in the hospital to treat exacerbations in participants with myasthenia gravis (mg). efgartigimod has been approved by the fda for ongoing (chronic) treatment of generalized mg in adult patients who are anti-acetylcholine receptor (achr) antibody positive but has not been studied in the treatment of worsening weakness requiring hospital admission (known as "exacerbation"). this investigation aims to see if using efgartigimod in this way improves symptoms and recovery from exacerbation, and how it affects certain mg markers in the blood. the main questions it aims to answer are: * is efgartigimod effective as a hospital-administered acute therapy for participants with worsening mg (mg exacerbation) who require hospitalization? * will efgartigimod lead to clinical improvement with a similar reduction in validated research scales, such as the quantitative mg (qmg) scale, as standard of care therapies? participants will receive 4 doses of efgartigimod over the course of 4 weeks with an additional follow-up visit at the clinic.

efgartigimod is thought to work by reducing circulating igg antibodies, including the antibodies that cause mg. one of the currently used treatments for mg exacerbation, called plasma exchange (plex), is also thought to work by reducing antibody levels by filtering blood through a machine similar to those used in dialysis for kidney failure. because of the similarities between how these two treatments work, there is reason to believe that efgartigimod may also be helpful in treating mg exacerbation.

Eligibility criteria:
inclusion criteria: * adults ≥ age 18 years with known generalized mg as identified by characteristic signs of generalized mg on clinical assessment and positive serology for achr antibodies as well as one of the following: 1. documented positive response to cholinesterase inhibitors such as pyridostigmine or edrophonium 2. abnormal decrement on slow repetitive nerve stimulation testing 3. abnormal single fiber emg * evidence of worsening weakness requiring hospital admission for stabilization and change in therapy as determined by a neuromuscular expert including: 1. quantitative myasthenia gravis (qmg) scale ≥ 11 2. mg-adl score ≥ 6 3. worsening weakness that is unlikely to be ameliorated by adjustment of current medications including impaired respiratory status, dysarthria, dysphagia, difficulty chewing, limb weakness, diplopia, ptosis. * ability to sign consent and be enrolled within 24 hours of hospital admission. for participants transferred to university of colorado hospital, the time of admission/presentation to the outside hospital is counted towards this 24-hour cap. exclusion criteria: * mg worsening thought to be related to active infection or due to medications (e.g. fluoroquinolone or aminoglycoside antibiotics, magnesium, chloroquine derivatives) * intubation prior to ability to sign informed consent or intubation within 24 hours of hospitalization * use of ivig within 2 weeks, or having undergone plasma exchange or received efgartigimod in the 4 weeks prior to admission * current ongoing use of ravulizumab or eculizumab (monoclonal antibody c5-complement inhibitors). * other medical conditions that, in the opinion of the investigator and treating clinicians, might interfere with the validity of assessment measures used in the study (e.g. steroid myopathy, cns pathology, severe arthritis, fractures, etc.). this criterion is a standard exclusion in mg trials and relates solely to other conditions that reduce muscle power or range of motion and would thus worsen scores on assessment measures like the qmg due to non-mg conditions. * known history of coagulopathy, blood clotting, recent severe bleeding (e.g. gi bleed). * pregnancy or breastfeeding. pregnancy must be excluded for all potential participants who are able to become pregnant prior to initiation of treatment. * igg levels \< 600mg/dl * evidence of active or chronic hepatitis b infection, untreated hepatitis c infection, hiv with low cd4 (\<200) count.

Keywords: myasthenia exacerbation efgartigimod